# HUMAN CARTILAGE PROTEASES IN ARTHRITIS

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 1987 · $148,566

## Abstract

The objective of the proposed research is to elucidate the enzymatic
mechanisms by which the extracellular matrix of human articular cartilage
is degraded.  Particular attention will be given to endogenous enzymatic
mechanisms under the control of the chondrocytes.  Proteolytic enzymes will
be studied with respect to the digestion of collagen and proteoglycan.  The
proteases of interest appear to be metalloproteases that act at
physiological pH.  They occur as active and latent forms; the latent forms
can be activated with trypsin or mercurials.  In the first stages of the
research, efforts will be directed to purifying the neutral
metalloproteases that degrade proteoglycan and to characterizing them with
respect to molecular weight, metal ion requirements for function and
stability, activation mechanisms, substrate specificity and action on
proteoglycan.  An inhibitor of metalloproteases has been detected in
cartilage and this will also be purified and characterized.  Collagenase,
gelatinase and the major enzyme activities will be quantitated in
osteoarthritic human cartilage by means of direct assay of tissue
homogenates involving endogenous substrates, and by extraction and assay of
the proteases on defined substrates.  The results will be correlated with
histochemical evaluation of the disease.  Similar studies will be performed
in the Pond-Nuki model of osteoarthritis in the dog.  Finally, organ
cultures of dog cartilage will be used to study the resorption of the
matrix induced by macrofactors and to test potential inhibitors and
therapeutic agents that might block matrix breakdown.  This work on
cartilage proteases and their regulation will be of considerable importance
in understanding the pathogenesis of joint disease, since it will define
the nature of the proteases actually within the cartilage, and possibly
arising from the chondrocytes.  The knowledge of enzyme properties and
specificities may open the way to rational treatment of joint disease.
This information may also be of value in understanding cartilage
remodeling, calcification, fracture healing, bone remodeling and
osteoporosis.

## Key facts

- **NIH application ID:** 3154926
- **Project number:** 5R01AR016940-15
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **SAM.gov UEI:** F8THLJQSAF93
- **Principal Investigator:** J. FREDERICK WOESSNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $148,566
- **Award type:** 5
- **Project period:** 1978-06-01 → 1988-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154926

## Citation

> US National Institutes of Health, RePORTER application 3154926, HUMAN CARTILAGE PROTEASES IN ARTHRITIS (5R01AR016940-15). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3154926. Licensed CC0.

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